The main objectives are to study the metabolism of the narcotic analgesic antagonists, naloxone and naltrexone. Studies were inititated with naltrexone where we were able to isolate and identify a major metabolite in urine as 6 Beta-OH naltrexone. It was also shown that this same reduction pathway occurs in the rabbit. However, in the chicken, another epimer, 6 alpha-OH naltrexone is obtained. We have developed the nuclear magnetic resonance approach to identify these 6 alpha and Beta compounds. In an analogous fashion, we have found that the 6 keto group in naloxone is reduced to yield stereospecifically 6 Beta-OH naloxone in the rabbit and 6 alpha-OH naloxone in the chicken. Since these species specific pathways indicate the occurrence of stereospecific enzymes, investigations are being conducted to compare and contrast the properties of the rabbit and the chicken enzyme system. The rabbit enzyme will also be used to biochemically prepare enough of the 6 Beta-OH naloxone and naltrexone to test their biological activity as agonists and antagonists.